Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 59 |
| INN | Trastuzumab deruxtecan, [fam]-Trastuzumab deruxtecan |
| Status | Approved |
| Drug code(s) | DS-8201, DS-8201a |
| Brand name | Enhertu |
| mAb sequence source | mAb humanized |
| General Molecular Category | ADC |
| Format, general category | Full length Ab conjugate |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | Glycine-Glycine-Phenylalanine-Glycine, Cleavable linker |
| Ave. DAR | 8 |
| Conjugated/fused moiety | Topoisomerase I inhibitor, DXd/DX-8951 (MAAA-1181a) |
| Discovery method/technology | None |
| Target(s) | HER2 |
| Indications of clinical studies | Colorectal cancer, gastric cancer, HER2+ breast cancer, Urothelial Carcinoma, Advanced solid tumors |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved EU, US, Japan, China, Australia |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | August 15, 2015 |
| Start of Phase 2 | August 25, 2017 |
| Start of Phase 3 | July 20, 2018 |
| Date BLA/NDA submitted to FDA | August 29, 2019 |
| Year of first approval (global) | 2019 |
| Date of first US approval | December 20, 2019 |
| INN, US product name | fam-Trastuzumab deruxtecan, (fam-trastuzumab deruxtecan-nxki) |
| US or EU approved indications | US: First approval for Breast Cancer (ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting). Supplemental approvals for: Brast Cancer (ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either: in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic: Hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting, or HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting; or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.); Non-Small Cell Lung Cancer (NSCLC) (ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.); Gastric Cancer (ENHERTU is indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.); HER2-positive Solid Tumors (ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options)) [as per January 27, 2025 label]. EU: First approval for Breast Cancer (ENHERTU as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti HER2 based regimens.). Supplemental approvals for: Breast cancer (HER2-positive breast cancer: ENHERTU as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens. HER2-low breast cancer: ENHERTU as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.); Non-small cell lung cancer (NSCLC) (ENHERTU as monotherapy is indicated for the treatment of adult patients with advanced NSCLC whose tumours have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy.); Gastric cancer (ENHERTU as monotherapy is indicated for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumabbased regimen.) [as per EPAR - Product information last updated on December 3, 2024]. |
| Company | Daiichi Sankyo Co. Ltd |
| Licensee/Partner | None |
| Comments about company or candidate | May 2020: AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been granted Breakthrough Therapy Designation (BTD) in the US for the treatment of patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received two or more prior regimens including trastuzumab. March 2020: Daiichi Sankyo Company, Limited announced the approval of ENHERTU (trastuzumab deruxtecan), a HER2 directed antibody drug conjugate (ADC), in Japan for the treatment of patients with HER2 positive unresectable or recurrent breast cancer after prior chemotherapy (limit the use to patients who are refractory or intolerant to standard treatments). Oct 17, 2019: AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) today announced that the US Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for [fam-] trastuzumab deruxtecan (DS-8201) and granted Priority Review. Trastuzumab deruxtecan has been granted US FDA Breakthrough Therapy Designation and Fast Track Designation for HER2-positive patients in the advanced or refractory breast cancer setting. September 9, 2019 I Daiichi Sankyo Company, Limited announced the submission of a New Drug Application (NDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for the use of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), for the treatment of patients with HER2 positive metastatic breast cancer. Marketing application submission(s) anticipated in H2 2019. Phase 3 study NCT03529110 recruiting as of July 20 2018; NCT03523585 in breast cancer recruiting as of Aug 1. NCT03329690 Phase 2 study in gastric cancer is considered a pivotal study. NCT03248492 Phase 2 in breast cancer recruiting as of Aug 25, 2017. Aug 2017: U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1) June 2017: Preliminary results from the dose expansion part of the phase 1 study of DS-8201 in a subgroup analysis of HER2-expressing metastatic breast cancer patients pre-treated with ado-trastuzumab emtansine (T-DM1) and pertuzumab demonstrated a 46.7 percent overall response rate (14 of 30 patients) and a 100 percent disease control rate (30 of 30 patients) to date. An overall response rate of 45.7 percent (16 of 35 patients) and disease control rate of 100 percent (35 of 35 patients) was observed in patients pre-treated with only T-DM1. The FDA has granted a fast-track designation for Daiichi Sankyo's DS-8201 as a treatment for HER2-positive unresectable and/or metastatic breast cancer in patients whose conditions progressed after treatment with HER2-targeted therapies. |
| Full address of company | Chuo City, Tokyo, Japan Asia Japan https://www.daiichisankyo.com/ |
Tetrapeptide-based linker; camptothecin drug. DAR = 8; DXd/DX-8951 is a Topoisomerase I inhibitor
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |